Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase
Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase
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DOI：
10.3233/prm-2010-0113
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发表时间：
2010-01-01
影响因子：
1.9
通讯作者：
Harmatz, Paul
中科院分区：
文献类型：
--
作者：
Decker, Celeste;Yu, Zi-Fan;Harmatz, Paul
背景与方法：生长衰竭是未经治疗的粘多糖病VI型（MPS VI: Maroteaux-Lamy综合征）的特征。在1/2期、2期、3期或3期扩展临床试验期间，研究了56名MPS VI患者（5至29岁）在每周以1mg /kg滴注重组人芳基磺化酶B （rhASB）之前和长达240周的生长情况。收集身高、体重和坦纳期数据。对合并数据进行分析，以确定治疗周的平均身高增长、青春期状态、基线尿GAG和治疗开始时的年龄对生长的影响。使用纵向模型分析治疗开始前后约2年的生长速率。结果：酶替代疗法（ERT）治疗48周后平均身高增加2.9 cm， 96周后平均身高增加4.3 cm。ERT上的生长与基线尿GAG无关。16岁以下的患者在接受治疗后身高增加最多。基于汇总数据的模型结果显示，与等效的预处理时间相比，ERT 96周期间的生长速率有显着改善。在进入临床试验的10例患者中发现青春期开始或进展延迟；所有患者在2年的ERT治疗中至少表现出一个Tanner期的进展，其中6人（60%）完成了青春期。结论：根据治疗周的平均身高分析和纵向模型分析显示，长期ERT治疗的MPS VI患者身高和生长速度明显增加。这种影响在16岁以下的患者中最大。身高增加可能是由于骨骼生长和/或关节收缩减少所致。骨骼生长和青春期延迟的解决可能与总体健康、骨细胞健康、营养、内分泌腺功能和炎症减少的改善有关。
Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling.Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty.Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.